There is a need for virucidal compositions which contain a minimum amount of active chemicals providing low toxicity, but which provide a fast and complete kill of resistant viruses on animate and inanimate surfaces. Very few chemical disinfectants are effective against resistant viruses when used at low concentrations in the range of from about 0.006% to 0.00125% (wt/vol.).
To measure the virucidal effectiveness of compositions, the work of Noll and Younger (Virology 8:319-343, 1959) suggested classifying viruses based on their affinity for lipids. Those viruses which easily combine with lipids, such as cholesterol, were called "lipophilic". Viruses which did not readily combine with lipids were called "hydrophilic". In 1963, Klein and Deforest (Proceedings, 49th meeting of Chem. Spec. Manuf. Assoc., page 116-118, New York) conducted a thorough investigation of the behavior of different types of viruses with several disinfectants. They found that the resistance of hydrophilic viruses to some germicides was based upon the failure of these germicides to react with hydrophilic viruses. Lipophilic viruses, on the other hand, were more susceptible to the inactivation of lipophilic germicides. Using three resistant hydrophilic viruses (Poliovirus Type 1, Coxsackie-virus B1 and Echovirus 6) and four lipophilic viruses (Adenovirus Type 2, Herpes Simplex virus Type Vacciniavirus and Asian Influenza virus), Klein and Deforest determined the lowest concentrations of germicides needed to inactivate these viruses in 10 minutes. Table 1 shows their results pertaining to the most resistant virus (Poliovirus Type I).
TABLE I ______________________________________ LOWEST CONCENTRATIONS (wt/vol. %) OF DISINFECTANTS INACTIVATING THE POLIOVIRUS TYPE 1 IN 10 MINUTES* ______________________________________ Sodium hypochlorite 0.02 Iodophor 0.015 Bichloride of mercury 0.2 Formalin 8.0 Glutaraldehyde 2.0 Ethyl Alcohol 70.0 Isopropyl Alcohol 95.0 Phenol 5.0 O-Phenyl Phenol 12.0 (neg.) Quaternary Ammonium 10.0 (24 hrs. contact neg.) ______________________________________
As previously demonstrated by Klein and Deforest (see Table I), phenols or phenol compounds such as ortho phenylphenol have little or no activity against hydrophilic viruses. In their study, Klein and Deforest showed, for instance, that an orthophenyl phenol concentration as high as 12% did not even kill the following viruses: Polio type 1, Coxsackie B-1 and Echo 6. Phenol itself needed concentrations as high as 5% to be active against the same three hydrophilic viruses. More recently, an independent laboratory study (Hazelton Biotech Corp., Project No. 2288-100, June 26, 1984), confirmed that a mixture of phenol with sodium phenate containing 0.51% of these compounds could not kill the Polio virus type 1, ATCC VR 192, according to EPA standards (DIS/TSS-7, Nov. 1981). It is apparent that high concentration of phenols or phenol compounds are needed to act upon resistant viruses. Conversely, phenol, phenol salts or phenolic compounds in the 0.5 to 5% concentration range are very toxic. Local damages to the skin include eczema, inflammation, discoloration, papillomas, necrosis, sloughing and gangrene (see Industrial Hygiene and Toxicology, Vol. 2, 1363-1408, second edition, Interscience Publishers, 1963). Monohalogenated phenols, or methyl phenols, or dimethyl phenols were shown to be as potent in promoting papillomas in animals as phenol itself Polychlorinated Biphenyls (PCB) have been banned by the EPA because they are extremely toxic even at low levels of concentration in the food chain.
More recently, other minimum germicide concentrations needed for inactivation in 10 minutes were determined (Journ. Hosp. Supp. Process. Distrib., Jan. 1985, pages 40-47) with Poliovirus Type 1 and 2. This data was collected by Dr. J. Bednarz-Prashad (University of Texas Medical School, Houston) using the standardized AOAC virucidal test approved by the Environmental Protection Agency (EPA Notice, DIS/TSS-7, Nov. 12, 1981). The results of this study showing the minimum concentration required to inactivate the virus with a 10-minute contact time are listed in Table II.
TABLE II ______________________________________ MINIMUM CONCENTRATION (wt/vol. %) TO INACTIVATE POLIOVIRUSES IN 10 MIN. (AOAC METHOD) ______________________________________ Chlorhexidine gluconate &gt;0.5* Glutaraldehyde + non-ionic 0.25 Glutaraldehyde + non-ionic + Glycol 0.19 O-Phenyl Phenol &gt;1.0* Glutaraldehyde-phenate &gt;0.14* ______________________________________ *This represents the lowest concentration of commercial product tested, virus was not inactivated at this concentration.
The minimum concentration of glutaraldehyde was eight times lower in Prashad's experiments than in Klein and Deforest's because Prashad used a glutaraldehyde activated by small amounts of non-ionic ethoxylates of isomeric linear alcohols (e.g, TERGITOL 15-S-12). In other words, as described in U.S. Pat. No. 3,968,248, and demonstrated by R. M. G. Boucher (Am. Journ. Hosp. Pharm. 31: 546-557, June 1974), the presence of small quantities of non-ionic surfactants can, in some cases, increase the cidal activity of glutaraldehyde solutions. Triethylene glycol was added to this same formula to make it odorless, and this glycolcontaining composition permitted a minimum glutaraldehyde concentration of 0.19% (wt/vol). This concentration is very close to the value observed using the glutaraldehyde solution containing the non-ionic ethoxylates without glycol. These prior results demonstrate a need for compositions exhibiting greater virucidal activity at low, relatively non-toxic, concentrations.
It is, therefore, an objection of the present invention to produce more potent virucidal solutions and decrease the amount of dialdehyde needed to destroy typical, lipophilic or hydrophilic viruses.
It is a further objective of the present invention to provide patent virucidal solutions which are formulated without phenols.